Disclosed are chelates resulting from the complexation of bifunctional do2pa derivatives ligands of formula (I), wherein the substituents R.sup.1, R.sup.1′, R.sup.2, R.sup.2′, R.sup.3, R.sup.3′, L.sup.1, L.sup.1′, L.sup.2 and L.sup.2′ are defined as in the claims, with metallic cations, especially Pb(II) and Bi(III). Also disclosed are bifunctional do2pa derivatives ligands of formula (I), as well as the use of chelates in nuclear medicine and the use of ligands in cations detection or epuration of effluents.

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The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a methyl group, and a coupling moiety terminating in a carboxylic acid group; b) coupling said octadentate chelator to at least one tissue-targeting moiety targeting HER2; and c) contacting said tissue-targeting chelator with an aqueous solution comprising an ion of at least one alpha-emitting thorium isotope.
A method of treatment of a neoplastic or hyperplastic disease comprising administration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided

Provided are compositions and methods for treating a solid cancer such as a HER3-positive tumor in a subject by administering an effective amount of a HER3-targeting agent labeled with a radionuclide such as .sup.225Ac, .sup.177Lu, .sup.131I, .sup.90Y, .sup.213Bi, .sup.211At, .sup.213Bi, .sup.227Th, or .sup.212Pb, alone or in combination with other therapeutic agents or modalities. The effective amount of the radiolabeled HER3-targeting agent may be a maximum tolerate dose administered in a single bolus or in fractionated doses that together equal the maximum tolerated dose.

Provided herein, inter alia, are radionuclide-labeled antibodies, immunocytokines, and methods for treating cancer using combination therapy with the radionuclide-labeled antibodies and the immunocytokines.

The production method of a radioactive metal-labeled antibody of the present invention includes a step of conducting a click reaction of a radioactive metal complex and an antibody site-specifically modified with a peptide to produce a radioactive metal-labeled antibody. The click reaction is performed between a first atomic group of the radioactive metal complex and a second atomic group directly or indirectly linked to the peptide. The second atomic group is an atomic group containing an azide group, or an atomic group containing trans-cyclooctene.

The present application provides an agent comprising or consisting of a binding moiety with specificity for a kallikrein protein (for example, PSA or hK2) for use in the treatment of prostate cancer, and a method for the treatment of prostate cancer in a patient, the method comprising the step of administering a therapeutically effective amount of an agent comprising or consisting of a binding moiety with specificity for a kallikrein protein to the patient.

This invention provides a compositions of matter comprising a therapeutic protein population (such as a HuM195 antibody population) wherein (a) each therapeutic protein in the population is conjugated to one or more actinium atoms, (b) each actinium atom is either .sup.227Ac or .sub.225Ac, and (c) the molar ratio of .sup.227Ac to .sup.225Ac in the composition is at least 1:1, This invention also provides related synthetic compositions and methods, as well as methods for treating hematologic malignancies.

Provided are compositions and methods for treating a solid cancer such as a HER3-positive tumor in a subject by administering an effective amount of a HER3-targeting agent labeled with a radionuclide such as .sup.225Ac, .sup.177Lu, .sup.131I, .sup.90Y, .sup.213Bi, .sup.211At, .sup.213Bi, .sup.227Th, or .sup.212Pb, alone or in combination with other therapeutic agents or modalities such as VEGF or VEGFR inhibitors. The effective amount of the radiolabeled HER3-targeting agent may be a maximum tolerated dose administered in a single bolus or in fractionated doses that together equal the maximum tolerated dose.

The present invention covers combinations of at least two components, component A and component B, comprising component A being PSMA-TTC, and component B being an antiandrogen selected form AR antagonists such as from cyproterone acetate, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide or keto-darolutamide, or an AR degrader such as ARV-110, or an ARN-terminal domain binder such as EPI-506, or an antisense oligonucleotide that reduces AR expression such as EZN-4176 or AZD-5312, or an androgen synthesis inhibitor such as abiraterone, particularly abiraterone acetate, seviteronel, galeterone, orteronel or ketoconazole, or a dual AR antagonist and androgen synthesis inhibitor such as ODM-204. Another aspect of the present invention covers the use of such combinations as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, particularly for the treatment of a hyper-proliferative disease.

The disclosure is directed to method of inhibiting cancer cell growth by contacting cancer cells with a dose of an anti-cancer agent that is divided equally between a nanoparticle carrier encapsulating the anti-cancer agent and antibody carrier that binds to a cancer-specific receptor and is conjugated to the same anti-cancer agent.